Musculoskeletal Path Flashcards
A 78 year old woman comes to her physician due to new onset continuous back pain. She is diagnosed with a vertebral fracture and the following is seen on her x-ray. What is her diagnosis- what caused this injury?
Osteoporosis:
Primary= more common
1. Type 1= post-menopausal; absolute increase in osteoclast activity due to estrogen withdrawal
2. Type 2= > 70 years, attenuated osteoblast function (no increase in osteoclast activity)
Secondary osteoporosis: Associated with other conditions:
- Endocrine (Cushing’s, hyperthyroidism, hypogonadism, iatrogenic steroids–> inhibited osteoblasts)
- Hematologic malignancies (Multiple myeloma–> activates osteoclasts
- Malabsorption (decreased Ca, Ph, Vit D)
- Alcoholism–> directly inhibits osteoblasts
A 58 year old man comes to his physician with increasing pain in his knees that worsens with activity. Suspecting arthritis, the physician orders an x-ray that reveals unusually dense bones. Additionally the man has had anemia refractory to iron supplementation. Based on these two clinical features, what is his possible diagnosis and treatment? What caused this pathology?
Osteopetrosis:
Marble bone disease: Albers-Schonberg disease
- Group of rare, heritable disorders; increased skeletal mass due to abnormally dense bone
- *Short, block-like radiodense bones on x-ray/CT**
- Radiopaque, 2-3 times normal weight
- WEAK bone due to disorganized structure (can’t remodel with stress)
- Calcified cartilage= weak, friable
- *Anemia due to replacement of marrow by sheets of osteoclasts, marrow fibrosis**
- Extramedullary hematopoeisis
- Pancytopenia
Blindness, deafness (foramen entraps nerves)
Treatment: bone marrow transplant, human IFN-gamma
- *Types:
1. **Autosomal recessive= severe, fatal to infants - Marked anemia, cranial nerve entrapment, hydrocephalus, infection
- Autosomal dominant= mild anemia/ asymptomatic
Pathogenesis:
- Failed osteoclastic bone resorption
- Mutation in osteoclast formation/function genes
- Defect in acidification of bone
- Mutations: TCIRG1 (AD- proton pump); CLCN7 (AR- Chloride channel), Carbonic anhydrase II (AR); transciption factors, cytokines causing osteoclast differentiation
- Primary spongiosum remains–> cartilage cores, thickened cortex, lack of funnelization of metaphysis
A 35 year old man with a 15 year history of Ulcerative Colitis fractures his arm after falling in a soccer game. The x-ray of his arm reveals decreased bone density. What is his diagnosis and what caused this?
Osteomalacia:
Inadequate bone mineralization of newly formed bone, cartilage matrix
- Adults and kids–> osteopenia
Causes:
- *- abnormal Vit D metabolism
- Intestinal malabsorption**
- Renal disorders
- Phosphate deficiency
- mineralization defects
Path:
- pseudofractures
- Exaggerated osteoid seams (osteoclast activity can’t occur, delayed calcification)
A 65 year old woman comes to her physician complaining of pain in her head and light headedness as well as arthritis. Her physician is concerned she may have migraines but on DXA scan she has extremely low bone density. X-ray reveals abnormal bone formation. Based on her clinical symptoms and her x-ray, what is her diagnosis and what other diseases could she develop?
Paget’s disease:
Pain (focal feature)
- Skull involvement (frontal/parietal)
- Pagetic steal–> light headedness (calvareal bone is stealing blood supply)
- Fractures/ arthritis
- High output cardiac failure (significant part of skeleton involved–> increased cardiac demands)
- Sarcomatous change, osteosarcoma in older patients (< 1%)
Chronic condition: bone enlargement and lytic lesions (disordered remodeling)
- uncoupling osteoblast/osteoclast activity
- See clast only activity, or blastic activity with patchy clast activity–> mosaic bone
- Seen in M & F > 60 years (3-4% in certain populations)
- Solitary or multiple sites
Pathogenesis: hereditary AD (chr 18)
- Sequestosome 1–> p62 protein in RANK pathway (more aggressive form)
- Viral nuclear inclusions similar to SSE (subacute sclerosing encephalitis)- giant cell tumor of bone
Path:
- “Hot” osteoclastic stage= lytic
- Mixed stage
- “cold” burnout stage: little activity
Histo:
- _Prominent cement lines (“mosaic”)
- Osteoclast= pathologic cell; “killer clasts” with 50+ nuclei (vs normal 8)_
- Can see sarcomatous change in < 1% (adult type of osteosarcoma)
A 68 year old woman with multiple recent fractures is at the orthopedist’s office for further evaluation of her condition. On x-ray there is a lesion in her bone that looks suspiciously different from her previous diagnosis of osteoporosis. A bone biopsy reveals atypia and hypercellularity. What is her diagnosis and what caused this?
Osteosarcoma due to Paget’s disease: sarcoma formation:
Pain (focal feature)
- Skull involvement (frontal/parietal)
- Pagetic steal–> light headedness (calvareal bone is stealing blood supply)
- Fractures/ arthritis
- High output cardiac failure (significant part of skeleton involved–> increased cardiac demands)
- Sarcomatous change, osteosarcoma in older patients (< 1%)
Chronic condition: bone enlargement and lytic lesions (disordered remodeling)
- uncoupling osteoblast/osteoclast activity
- See clast only activity, or blastic activity with patchy clast activity–> mosaic bone
- Seen in M & F > 60 years (3-4% in certain populations)
- Solitary or multiple sites
Pathogenesis: hereditary AD (chr 18)
A 35 year old Asian woman presents with a fracture in her arm with no previous trauma. An x-ray reveals a lobulated, lytic lesion. Bone biopsy reveals the following cell type. What is her diagnosis and treatment?
Giant cell tumor:
Locally aggressive
-20s-40s F > M, Asians
- Site: epiphysis, metaphysis of long bones
Clinical: pain, path fractures
X-ray: lytic, multilobulated “soap bubble”
Gross: Blood-filled sponge
Histo: mononuclear spindle-shaped cells and mononucleated giant cell tumors
Treatment: curettage, recur (50%), 10-15% lung mets
Osteochondroma
Developmental defect (hamartoma) at epiphyseal plate
- “Ring of Ranvier”
- Cartilage capped growth growing away from joint
Hereditary multiple osteochondromatosis:
- Extra genes on Chromosomes 8, 11, 19–> chondrocyte proliferation and differentiation
A 15 year old boy is brought to his family physician due to increasing pain in his hip. An x-ray revels a lytic lesion in the head of his femur. Additionally his alkaline phosphatase levels are elevated on a blood panel. He is sent to a surgeon to have the head of the femur replaced. Based on the specimen and the woven bone with atypical osteoblasts found within, what is his diagnosis?
Osteosarcoma
Most common PRIMARY malignant bone-forming tumor (most common bone tumor= metastatic)
- 2nd decade, M > F
- Rb gene mutation in 2/3; p53
Sites: metaphysis of femur, tibia > humerus
X-ray: lytic, sunburst pattern, codman’s triangle
Clinical: Pain, increased alk phos
Histo: woven bone (osteoid) with malignant osteoblasts
Variants:
- Parosteal
- Periosteal
- Telangiectatic
A 15 year old boy presents with pain and swelling in his femur. A bone biopsy revelas the following small round blue cells that stain positive for CD99 and PAS. What is his diagnosis and treatment?
Ewing sarcoma:
Uncommon
- 2/3 < 20 years, M > F (2:1)
- Reciprocal translocation t(11;22)(p13;q12), PNET family
Clinical: pain, swelling
X-ray: midshaft/diaphysis of long bones; “onion skin pattern”
Histo: small round blue cell tumor
- PAS, CD99
- t(11;22) or t(21;22)
Treatment:
- Chemo/radiation
- surgery
- 60-75% 5-year recurrence rate
A 15 year old boy presents with pain and swelling in his femur. A bone biopsy revelas the following small round blue cells that stain positive for CD99 and PAS. What is his diagnosis and treatment?
Ewing sarcoma:
Uncommon
- 2/3 < 20 years, M > F (2:1)
- Reciprocal translocation t(11;22)(p13;q12), PNET family
Clinical: pain, swelling
X-ray: midshaft/diaphysis of long bones; “onion skin pattern”
Histo: small round blue cell tumor
- PAS, CD99
- t(11;22) or t(21;22)
Treatment:
- Chemo/radiation
- surgery
- 60-75% 5-year recurrence rate
A 42 year old man is treated by his physician for pain in his hip. A CT-scan reveals a lesion in his pelvic bone with calcification and lytic lesions. Histological samples reveal the following. What is his diagnosis?
Chondrosarcoma:
2nd most common primary malignant bone tumor
- M > F, 4th-6th decade
- Some from cartilage enchondromas
- Variants classified by location
- Can see molecular trisomy 7, rearrangement of chrom 17
* extracellular sarcoma mixoid type: (9;22)(q31;q12)
Sites:
- Axial, proximal femur, humerus
X-ray: lucent or ring-like; calcified and lytic areas
Histo: grading based on cellularity, degree of atypia
A 77 year old woman visits an orthopedist due to recurrent, worsening knee pain that now restricts her daily activities of living. Based on the imaging below, what is her diagnosis?
Primary osteoarthritis:
Most common form of joint disease
- Slow, progressive
- Seen in articular cartilage of weight bearing joints, fingers
- Older patients (or young following trauma)
- Primary osteoarthritis:
Unknown etiology; several postulated factors:
- increases with age
- 85% of patients age 75-79
- < 45 years= male predominant; > 55 years= females
- Hereditary factors? - Secondary osteoarthritis:
Known etiology
Clinical:
See joint space narrowing, subchondral bone thickening, painful joint
- Pain follows activity
- Restriction of motion
- Lab findings unhelpful
- Supportive therapy
Pathology:
- Seen at DIP, PIP of upper extremity; knees, hips, cervical and lumbar spin
- Narrowing of joint space on x-ray
- Increased subcondral bone, bone cysts
- Osteophyte formation
Histology:
- Earliest= death of articular cartilage
- Cracking, fibrillation
- Reactive bone/cartilage–> fibrocartilage plug
- Eburnation (loss of articular cartilage- BELOW), subchondral bone cyst (decreased density on x-ray), osteophyte (dense bone formation with cartilage cap, continuous marrow)
A 77 year old woman visits an orthopedist due to recurrent, worsening knee pain that now restricts her daily activities of living. Based on the gross specimen below, what is her diagnosis?
Primary osteoarthritis subchondrial cyst:
Most common form of joint disease
- Slow, progressive
- Seen in articular cartilage of weight bearing joints, fingers
- Older patients (or young following trauma)
- Primary osteoarthritis:
Unknown etiology; several postulated factors:
- increases with age
- 85% of patients age 75-79
- < 45 years= male predominant; > 55 years= females
- Hereditary factors? - Secondary osteoarthritis:
Known etiology
Clinical:
See joint space narrowing, subchondral bone thickening, painful joint
- Pain follows activity
- Restriction of motion
- Lab findings unhelpful
- Supportive therapy
Pathology:
- Seen at DIP, PIP of upper extremity; knees, hips, cervical and lumbar spin
- Narrowing of joint space on x-ray
- Increased subcondral bone, bone cysts
- *- Osteophyte formation**
Histology:
- Earliest= death of articular cartilage
- Cracking, fibrillation
- Reactive bone/cartilage–> fibrocartilage plug
- Eburnation (loss of articular cartilage), subchondral bone cyst (decreased density on x-ray), osteophyte (dense bone formation with cartilage cap, continuous marrow)
A 77 year old woman visits an orthopedist due to recurrent, worsening knee pain that now restricts her daily activities of living. Based on the histologic sample below, what is her diagnosis?
Primary osteoarthritis: osteophyte:
Most common form of joint disease
- Slow, progressive
- Seen in articular cartilage of weight bearing joints, fingers
- Older patients (or young following trauma)
- Primary osteoarthritis:
Unknown etiology; several postulated factors:
- increases with age
- 85% of patients age 75-79
- < 45 years= male predominant; > 55 years= females
- Hereditary factors? - Secondary osteoarthritis:
Known etiology
Clinical:
See joint space narrowing, subchondral bone thickening, painful joint
- Pain follows activity
- Restriction of motion
- Lab findings unhelpful
- Supportive therapy
Pathology:
- Seen at DIP, PIP of upper extremity; knees, hips, cervical and lumbar spin
- Narrowing of joint space on x-ray
- Increased subcondral bone, bone cysts
- Osteophyte formation
A 50 year old man with a 20-year history of rheumatoid arthritis comes to the emergency room with a painful swelling in his calf (below). Based on his condition, what could possible be occuring and what is he as risk for?
Rheumatoid arthritis of the knee: Ruptured Baker’s cyst
Clinical presentation:
Bilateral, symmetrical
Large and small joints
Inflammation of the synovium
Fluid accumulation in the joint
Joint swelling and pain
If not diagnosed and treated vigorously–> destruction, deformity, disability
- *Knee**
- Synovitis causing Baker’s cyst (rupture-DVT)
Epidemiology:
Relatively common disorder
- Affects >1% of the population of North America
- Female:male 2.5:1
- Incidence increases with age (Peak: 4th-6th decade)
Associated with shortened life expectancy
Constitutional symptoms: LGF, wt loss, anorexia, fatigue
Extra-articular involvement:
- Lungs, skin, heart, hematologic, eye, vessels
- Rarely: CNS (rheumatoid nodules), kidneys
- Differentiate from drug side effect!
A 30 year old woman presents to her physician with worsening joint pain over the last 6 months, especially in her knees. She noticed some pain and swelling in her hands but thought it was related to her work in a dressmaker’s shop, but now her knees are hurting as well. Based on gross specimens below, what types of changes are occuring and what is her possible diagnosis?
Rheumatoid arthritis: Articular cartilage destruction from periphery of joint (central sparing
Below: Papillary synovial hyperplasia, subsynovial lymphoplasmacytic infiltration
- *Pathophys**:
- Overactive T cells–> attack synovial fluid space–> Synovial inflammation:
- Fluid filled with neutrophils
- Pannus infiltrated by T lymph, macrophages, fibroblasts, plasma cells, endothelial dendritic cells
- -> chronic inflammation
- –> Bone, cartilage, ligament, tendon damage
- -> erosions, joint deformity
Treatment:
Goal is complete remission
1. Start with anti-inflammatory medications
- NSAIDs
- Corticosteroids
2. Add immunomodulators (DMARDs) early
3. If no significant improvement in first few months add “biologics”
- Antibodies against inflammatory cytokines
A 45 year old woman with a 20 year history of rheumatoid arthritis comes to the emergency room with the following necrosis in her fingertips. Additionally she has a marked footdrop. What is occuring and what is her treatment?
RA vasculitis: extremity and nerve involvement:
Overactive T-lymphocytes infiltrating and destroying capillary structures supplying fingertips, nerves
Vasculitis
- Arterioles, capillaries, venules
- Mostly leukocytoclastic vasculitis
- Skin ulcerations (necrotizing)
Nervous system:
- Myelopathy
- Mononeuritis multiplex:
- disorder characterized by simultaneous or sequential damage to more than one nerve group
- isolated damage to at least 2 separate nerve areas
- involves destruction of the axon
- interferes with nerve conduction at the location of the damage (see wrist, foot drop)
- causes include a lack of oxygen caused by decreased blood flow or inflammation of blood vessels. No cause is identified for about one-third of cases
Treatment:
Goal is complete remission
1. Start with anti-inflammatory medications
- NSAIDs
- Corticosteroids
2. Add immunomodulators (DMARDs) early
3. If no significant improvement in first few months add “biologics”
- Antibodies against inflammatory cytokines
A 65 year old woman with a 40-year history of rheumatoid arthritis presents to her physician with the followin in her eye. What has occured? Additionally, she has been having increasing difficulty breathing. What might be causing her breathing problems?
Rheumatoid arthritis: extra-articular manifestations:
Front: Ocular
- Keratoconjunctivitis sicca (also seen in Sjogren’s)
- Episcleritis (more superficial than scleritis)
- Scleritis
- Scleromalacia perforans (rheumatoid nodule)
Below:
Pulmonary
- Pleural disease
- Interstitial lung disease
- Pulmonary nodules
Below is a histological specimen from the PIP joint of a 40 year old woman with a history of RA. What is present in her joint that is abnormal and how might it be contributing to her symptoms?
Rheumatoid Arthritis: Pannus:
Granulation tissue formation over joint space (arthritis) or over cornea, etc.
Pathophys:
- Synovial inflammation:
- Fluid filled with neutrophils
- Pannus infiltrated by T lymph, macrophages, fibroblasts, plasma cells, endothelial dendritic cells
- Leads to articular cartilage and juxta-articular bone loss
- *Front**: Pannus overlying articular cartilage
- *Back**: hyperplastic synovium of pannus
A 50 year old woman with a 30 year history of rheumatoid arthritis presents to her physician after noticing a nodule on her elbow that is giving her some pain. The nodule is biopsied and the following is found. What is it and why did it form?
RA nodule (extra-articular):
Subcutaneous nodules at areas of pressure (skin on elbows, legs)
- Moveable, firm, rubbery, occasionally tender
- *Front**: rheumatoid nodule with central fibrinoid necrosis
- *Below**: Palisaded macrophages surrounding rheumatoid nodule
The same 45 year-old caucasian female also complains that she has to drink water more frequently, not because she is thirsty, but because she is unable to swallow food or speak properly without doing so. Exam of her tongue revelas the following. What other oral manifestations would be seen in Sjogren’s?
Sjogren’s: oral involvement:
Dry mouth (xerostomia)–> decreased saliva
- Difficulty swalling food, inability to speak, change in taste, burning sensation, increased in dental caries
- Physical exam: dry, erythematous, sticky oral mucosa, dental caries, scanty/cloudy saliva, angular chelitis
- Parotid, major salivary gland enlargement in 60% patients (episodic or chronic, unilateral–> bilateral)
Complications:
- accelerated caries, loss of dentition, poor fitting dentures,
- oral candidiasis (yeast infection with Candida albicans),
- sialolithiasis (salivary gland stones),
- sialostenosis (salivary gland strictures),
- bacterial sialadenitis (infection),
- disturbed sleep (related to nocturnal fluid ingestion),
- depression and weight loss (related to oral discomfort, dysphagia etc.).
Diagnostic questions:
- Symptoms of dry mouth for at least 3 months?
- Recurrent or persistently swollen salivary glands?
- Need for liquids to swallow dry foods?
Objective documentation of dry mouth
- Oral examination: diminished salivary pool, loss of glistening of tongue, mucous membranes, erythema, fissures on tongue
- Sialometry: Measure salivary flow using Lashley cup; circular cup connected to plastic tube, collect parotid saliva (placed over Stensen’s duct)- normal resting = 0.1 ml/min, after citric acid = 0.5-1.5 ml/min
- Salivary scintigraphy: nuclear medicine test to measure isotope uptake into glands (saliva formation) plus stimulated salivary discharge
- Sialography: inject contrast medium into salivary ducts followed by routine x-rays (MRI)
Confirmation of histologic involvement by salivary gland biopsy (below)
- Labial minor salivary gland biopsy on inner aspect of lip
- Findings: focal lymphocytic sialadenitis= accumulation of 50+ mononuclear cells around salivary gland acini, ducts
1. Divide number of foci by glandular surface area= focus score
2. Focus score > 1/4 mm3= Sjogren’s
A 45-year old caucasian female comes to her physician complaining of persistant dry eyes. On exam it is noted that her eyes appear red and there is destruction of the conjunctival epithelium. What other tests can be done to test for pathological dry eyes and what other symptoms would indicate Sjogren’s Syndrome?
Sjogren’s keratoconjunctivitis, dry eye:
Chronic inflammation of lacrimal glands:
- produce decrease in tear production
- Diminished tear production leads to the destruction of both corneal and conjunctival epithelium and a constellation of clinical findings termed keratoconjunctivitis sicca (KCS).
Physical signs:
- Dilation of the conjunctival vessels, pericorneal injection, (red eye)
- Irregularity of the corneal image and
lacrimal gland enlargement.
- The patient usually complains of a burning, sandy or scratchy sensation under the lids, itchiness, redness and photosensitivity.
- Failure to treat dry eyes may result in complications such as corneal ulcers or melting, corneal perforation, loss of vision, bacterial conjunctivitis or blepharitis (inflammation of the eyelids).
Diagnostic questions:
- Symptoms of dry eyes for at least 3 months?
- A foreign body sensation in the eyes?
- Use of artificial tears 3 or more times per day?
Objective documentation of dry eyes
- Schirmer’s test (below): measures tear production on strip of paper in eye duct (normal > 10mm/5 min)
- Rose Bengal/ fluorescien corneal staining: ocular surface irregularity or damage due to dryness
- Tear break film test: tear film stability between last blink and appearance of dark, non-fluorescent areas in tear film (normal > 10 seconds)
- *Diagnosis of Sjogren’s syndrome**:
1. Dry mouth: documentation
2. Dry eyes (document via above tests)
3. Autoantibody presence: - Positive ANA, Rheumatoid Factor (> 1:160)
- Positive anti-SSA (Ro) or anti-SSB (La)
4. Salivary gland biopsy for histologic involvement
A 40 year old obese man comes to his physician because he developed a recent onset of excruciating pain in his left big toe (below). This has never happened to him before and there was no trauma to his foot. What might his diagnosis be and how would this be confirmed?
Acute gouty attack:
Acute attack
- Abrupt, monoarticular
- Involves MTP –> ankle, tarsal joint, knee, wrist, elbow
- Exquisite tenderness, swelling, warmth
- Fever, leukocytosis may occur
- Overlying skin desquamates
- Lasts 3-10 days w/o treatment
Precipitating event of acute attack:
- Trauma, surgery, stress, infection, food (red meat, shellfish), alcohol (beer)
- Diuretics, low dose aspirin
- *Diagnosis of Gout: Urate crystals:**
- Crystal in the aspirate:
- Monosodium urate monohydrate= needle shaped
- Differentiate from calcium pyrophosphate dihydrate (pseudo-gout)- NOT needle shaped
- Crystal aligned with polarizer= yellow
- Perpendicular to polarizer= blue
- Negative birefringence (vs CPP= positive birefringence)
- Crystal inside neutrophils= acute gout attack
A 60 year old man with a history of recurrent gout comes to his physician who notes the following on his ear. What is this a symptom of and how is the diagnosis confirmed?
Chronic Gout tophi: deposition of urate crystals (below)
Acute arthritis; inflammatory response to MSU (urate) crystals in joints
- Generally starts in 1st MTP joint (big toe)
- Peripheral joints, tendons, any tissue
- Recurent
- Chronic, deforming
- Males/post-menopausal women
- Associated with Lesch-Nyhan syndrome: mutations in the HPRT gene located on X chromosome–> HGPRT enzyme defect–> uric acid buildup
Pathophys:
- Sodium urate triggers immediate immune response (potent trigger)
- Leads to production of IL-1–> inflammatory cascade
- Cells move to site of urate deposition
- Cannot remove urate
- Eventually immune response tapers
Clinical presentation of Chronic gout (tophaceous gout):
Result of:
- Years of persistent hyperuricemia
- Frequent attacks
- Inadequate therapy
Features of chronic gout:
- Joint destruction
- Tophi: subcutaneous tissue, tendons, IP-MCP joints, pinna of ear
- Extra-articular: myocardium, pericardium, aortic valves, extra-dural spinal, kidneys
- May mimic RA but less symmetrical
A 35 year woman comes to her physician after vacationing with her family because she developed a horrible rash on her face and neck. What is possible cause of the rash and how frequently is this the first manifestation of this disease?
SLE: cutaneous manifestations
- *Front**: photosensitivity rash (both cutaneous and overall ill-feeling when exposed to sunlight)
- *Below**: Malar rash: Fixed erythema, flat or raised, sparing the nasolabial folds
SLE: primary manifestations:
- Arthritis (55%)
- Skin involvement (25%)
- Nephritis (5%)
- Fever (5%)
- Other (15%)
What is the phenomenon noted below in a patient diagnosed with systemic lupus? What is the epidemiology of her disease?
SLE- Jaccoud’s arthropathy:
Early onset: Finger alignment appears abnormal but can be manipulated back into normal position
Later onset: permanent deformity
- Incidence of 1.8 to 35 cases per 100,000/ year in general population
- Prevalence fluctauates from 250000 to 1.5 million cases of lupus.
- Women>Men – 9:1 ratio
- African Americans>Hispanics>Whites
- Usual onset between 15-45 years (60% cases)
Below is a patient being seen for Systemic lupus. What type of deformity is apparent and what caused these changes?
SLE: discoid rash: Raised patches, adherent keratotic scaling, follicular plugging; older lesions may cause scarring
Etiology is unknown
• SLE is an autoimmune disease
• Genetic factors
– HLA association (HLA DR2/HLA DR3)
• Environment factors
– Sunlight, drugs, chemicals, foods
– Bacterial or viral infections
– More associated with flares and exacerbations
• Hormonal factors
– Increased estrogen and prolactin levels
- Flares during pregnancy (vs RA)
Immune changes:
- Abnormal complement components (C1q, C4, etc )
- Fc Receptor abnormalities
–> delay in clearing dying (apoptotic) cells, exposing more autoantigens.
A 16 year old girl with SLE is brought to her physician because of a new onset of rash and papules in her mouth. Her mother is worried about the progression of her daughter’s condition and wants to know what other manifestations may occur. What might happen in a lifetime of SLE?
SLE: bullous lesions
Joints 90%:
- Arthritis and/or artharlgias are the most common presenting manifestation of SLE
- Most cases: Symmetrical.
- Unlike RA, is usually non-erosive ( at xrays) w/ subluxations, initially reversible.
- Involve periarticular surfaces.
- Increase frequency of tendon rupture.
- Fibromyalgia can overlap joint sx.
Skin
- Rashes 70%: butterfly rash, interarticular dermatitis, palpable purpura
- Discoid Lesions 30%: erythematous, hyperpigmented; flattened; scarred central areas with thin/fragile epidermis; follicular plugging
** Discoid lupus can become systemic lupus
- Alopecia: diffuse 40%
Pleuropericardium 60%
- Serositis: pleuritic pain more frequent than effusions
- Fluid exudative with normal glucose
Pulmonary manifestations:
- Pneumonitis
- Pulmonary hemorrhage (small capillary leak)
- PAH
- Shrinking lung syndrome (diaphragm, respiratory muscles)
Cardiac manifestations:
- Most common cause of mortality in SLE is CAD
- Endocarditis in 15-60% (asymptomatic)= Libman-Sacks endocarditis
- Myocarditis in 9%: mild, seen as diastolic dysfunction
- Clots in placental tissue–> miscarriages
Kidney 50%
Raynaud’s 20%
Mucous Membranes 15%
CNS (Seizures/Psychosis) 15%
A 50 year old woman has been suffering from SLE for 20 years and comes into her physician with increasing problems breathing. An MRI reveals the following. What is occuring with her lungs?
SLE: pulmonary manifestations
“Shrinking lung syndrome”
Pulmonary manifestations of SLE:
- Pneumonitis
- Pulmonary hemorrhage (small capillary leak)
- PAH
- Shrinking lung syndrome (diaphragm, respiratory muscles)
A 45 year old man with a 20-year diagnosis of SLE comes to his physician for a physical. His urine sample reveals elevated protein levels. Based on the histology below, what is his diagnosis and what types of changes are seen in kidneys in patients suffering from lupus?
SLE: lupus nephritis
Class I: Normal glomeruli
a) Nil by all techniques
b) Normal by light but deposits on EM or IF
Class II: Mesangial glomerulonephritis: mesangial cells affected
Class III: Focal glomerulonephritis: endothelial cells affected
Class IV: Diffuse glomerulonephritis: endothelial cells affected
Class V: Diffuse membranous glomerulonephritis: epithelial cells affected
Class VI: Advanced sclerosing glomerulonephritis
Lupus nephritis:
Anti-DNA Antibody deposition, complement activation will produce inflammation, occlusion and disruption of glomeruli that translate in:
- Protein urinary excretion (Nephrotic Sd)
- Hematuria (Nephritic Sd)
- Increase on Creatinine levels
- Renal Failure
A 65 year old woman with a history of SLE expired from a Myocardial ischemic attack. On autopsy the following is found in her coronary valves. What has occured and did this cause her heart attack?
SLE: Libman Sack’s Endocarditis:
Cardiac manifestations:
- Most common cause of mortality in SLE is CAD
- Endocarditis in 15-60% (asymptomatic)= Libman-Sacks endocarditis
- Myocarditis in 9%: mild, seen as diastolic dysfunction
- Clots in placental tissue–> miscarriages
A 55 year old man with a 20 year history of smoking 2 packs a day is diagnosed with small cell lung carcinoma. 3 weeks after his diagnosis he develops a rash on his face. His oncologist believes it is related to his treatment but the patient also complains of exercise intolderance and muscle pain. A muscle biopsy reveals the following. What is his diagnosis and what was the pathogenesis of this disease?
Dermatomyositis
Afflicts children and adults
- Characteristic rash affecting the upper eyelids, face, and trunk
- Increased association with an underlying malignancy (usually carcinoma) in males
- Polymyositis and inclusion body myositis have a much reduced risk of underlying malignancy compared to dermatomyositis in adults.
Pathogenesis:
- Immune complex formation with IgG, IgM and complement including C5-9 membrane attack complexes in the walls of blood vessels
- NOT direct attack on muscle; also affects dermis as vascular attack occurs here too
Histology:
- *- Microangiopathy with loss of capillaries,
- **perifascicular atrophy****
- Perivascular infiltrates of B and T cells, predominance of CD4+ T cells
- Muscle infarcts
- Skin rash also related to the microangiopathy
- All fibers at edge of fascicle shrivel up
- Look for complement deposition in capillaries
A 40 year old woman with Raynaud’s develops pain and weakness in her legs which is worse with exercise. A muscle biopsy below reveals lymphocytes within her muscle fibers causing damage. What is her diagnosis?
Polymyositis:
Inflammation focused on the muscle fibers themselves:
- No microangiopathy as in dermatomyositis
- Perifascicular atrophy absent
- CD8+ T cell mediated cell injury
- Frequent association between anti-Jo-1 (recognizes a histidyl-tRNA synthetase) as well as interstitial lung disease, Raynaud phenomenon, and nonerosive arthritis
Below: necrosis and regeneration of muscle tissue
A 45 year old man presents to your office due to a new onset of pain and cracking at the edge of his lips that he has tried treating at home with neosporin but won’t go away. Additionally he has a 5-year history of HIV infection. Based on his clinical presentation (below), what is his diagnosis and what would be the histological presentation?
Oral candida infection
The most common fungal infection in the oral cavity and oropharynx
- In many cases other factors play a role: antibiotic therapy, immunosuppression, xerostomia, anemia
Clinical presentation: varies : asymptomatic, pseudomembranous (thrush), erythematous, angular cheilitis (red, scaling, fissuring area at the corners of the mouth)
Histopath:
Fungal hyphae or pseudophypahe and ovoid spores (PAS positive) associated with neutrophilic microabscess
On exfoliative cytology or tissue sections
A 36 year old man presents to his physician after experiencing fever and general malaise over the past 6 days. On physical examination, a blister is noted on his lip that he states appeared around the time of his feeling ill. What does he likely have and what would be visible on histology?
- *Herpes simplex virus 1 infection**:
- First exposure to HSV1: 90% of patients have subclinical symptoms, 10% of patients develop primary herpetic gingivostomatitis
Herpetic gingivostomatitis: fever, malaise, lymphadenopathy, mucosal erythema, vesicles and ulcers that resolve in 7 to 14 days.
- *Latent virus** within trigeminal ganglion reactivates and results in infection of the vermilion border of the lip (herpes labialis, “fever blister”, “cold sore”)
- Cluster of fluid-filled vesicles which rupture, crust and heal within 7-10 days.
Histopath:
Nuclear enlargement of infected cells
Condensation of the chromatin at the periphery of the nucleus
Multinucleated cells formed by fusion of infected cells
Inflammation and edema of adjacent mucosa
A 33 year old woman goes to her physician for a sore throat. On exam, there are abscesses noted in her tonsillar crypts. Histologic exam of a specimen reveals the following. What is her diagnosis?
Actinomyces infection:
Saprophitic, Gram positive anaerobic bacteria part of the normal flora
- Colonize tonsillar crypts, dental plaque, gingival sulci
Acute form: painful abscess
Chronic form: extensive fibrosis (hard, wooden induration), fistula formation, periostitis, osteomyelitis
Histo: Colonies of club-shaped filaments arranged in a rosette pattern surrounded by neutrophils
Granulation tissue
Can occur in patients after radiation therapy–> chronic osteomyelitis due to actinomyces infection
A 50 year old man is referred to an oral maxillofacial surgeon after finding the following abnormality in his mandible on X-ray at the dentist. The abnormal tissue is ressected and shows enamelly-derived tissue and odontogenic epithelium. What type of tumor is it and what is the common treatment?
Ameloblastoma:
Tumor arises from enamel organ or progenitor cell lines
- Develop soft tissue components of odontogenic epithelial
- Benign, slow-growing, locally inasive
- Arise in mandibular ramus, maxilla, floor of nasal cavity
Histo:
- Islands of proliferating odontogenic epithelium reminiscent of enamel organ
- Basophilic columnar cells at periphery with reverse polarization (nuclei away from basement tissue)
- Edematomous cells in nests or cords
Treatment:
- Wide surgical ressection
- Long-term follow up due to 25-55% recurrence rate
A 35 year old woman presents to her physician after a dentist appointment where the dentist discovered a mobile mass in her left parotid gland. The mass was excised and the following was discovered. What is the most likely diagnosis and treatment? What is the prognosis?
- *Pleomorphic adenoma of salivary gland**
- MOST COMMON salivary glands neoplasm
- Most commonly in the PAROTID followed by minor salivary glands
- Wide age at presentation
- PAINLESS, slowly growing mass, mobile
- Paresthesia due to nerve compression - rare
Histo:
- Well-circumscribed, variably encapsulated mass
- Multinodular (esp. in recurrent disease)
- Composed of three cell types:
1. Epithelial glandular ductal structures
2. Myoepithelial cells
3. Mesenchymal stroma: myxoid, chondroid, hyalinized, osseous - *Treatment:**
- Surgical excision
- *Prognosis**:
- Recurrence rate: 45% after simple enucleation (due to lack of encapsulation or incomplete removal)
- Recurrence rate: 2.5 % with superficial or total parotidectomy
- Malignant transformation – in 2-7%
The following histologic specimen was obtained from a parotid gland mass. There was a similar mass on both parotid glands (bilateral). Based on the appearance, what is the diagnosis, treament and prognosis?
- *Warthin’s tumor**:
- Second most common benign salivary gland tumor
- Characteristically presents in the parotid
- Bilaterality or multifocality occurs more frequently than any other tumor, and it is synchronously identified with other tumors more than any other tumor type
- *Histo:**
- Circumscribed, solid/cystic. Cysts may contain yellow-brown fluid.
- Papillary fronds and cystic spaces lined by double layered oncocytic epithelium
- Dense lymphoid node-like stroma intimately associated with the epithelial component
- *Treatment:**
- Surgical excision
- *Prognosis:**
- 4-25% recurrence due to multifocality or incomplete excision
A 46 year old man presents to his physician for a physical. He notes a recent development of a painless blister on the inside of his lip. He thinks it may be related to having accidentally cut his lip while eating nuts a few weeks ago. What is his diagnosis and treatment?
Salivary Mucocele
The most common non-neoplastic lesion of salivary glands
- “Pooling of mucin in a cystic cavity”
Types:
- Retention type – mucin pooling confined within a dilated excretory duct
- Extravasation type – escape of mucin from the duct system into connective tissue – most common type
Seen in: lower lip, tongue, floor of mouth, palate
Presentation: soft, fluctuant semitranslucent painless swelling that may occur after a traumatic event
Treatment - complete excision, including minor salivary gland
A 47 year old woman presents to her doctor because of increasing issues with her mouth and eyes. She says she feels like her eyes are dry all the time, even when she uses eye drops, and she has to drink lots of water to be able to swallow any food because she doesn’t make enough saliva. Based on these two symptoms and the biopsy of one of her salivary glands (below), what is her diagnosis?
Sjogren’s salivary gland:
Describes a characteristic lymphocytic infiltrate in salivary glands; doesn’t commit to an etiologic cause but describes histologic findings
Most cases – women in the 4th and 5th decades
- Associated with or is a precursor of Sjogren’s syndrome
- *Two types:
1. Systemic: collagen vascular disease
2. Localized to salivary and lacrimal glands**
Pathology:
- Uni or bilateral enlargment of parotid glands with preserved lobulation
Histo:
- Periductal chronic inflammation extending into acini
- Glands replaced by polyclonal lymphocytes, germinal centers, plasma cells
- Lesion= lymphoepithelial sialadenitis (epimyoepithelial islands)
- Similar changes present in minor salivary glands in Sjogren syndrome (biopsy smaller glands first)- need clinical diagnosis and serologic specimen to confirm dx
A 56 year old woman complains of a recent onset of pain in her cheek. The pain is exacerbated by eating or smelling food. An MRI reveals a calcification in her salivary gland and the following is removed. What is in her salivary gland?
Salivary gland sialolithiasis:
Collection of concretions which form a stone within the salivary gland excretory duct system (stone in duct)
- Most common involves the submandibular gland (Wharton’s duct) and may cause a chronic sialadenitis distal to the stone.
- Always visible on radiographic examination
- Nidus of cellular debris in the center of concentric laminated calcium deposits
Below is a specimen from the nasal sinuses of an otherwise healthy 23 year old man. He complains of recent worsening of his seasonal allergies after avoiding going outside in the spring. Based on the histology, What is his diagnosis?
- Hypersensitivity reaction to fungal antigens (atopic patients), aspergillus
A 54 year old man with a history of chronic recurrent sinusitis presents to an ENT to have his sinuses examined. A ball of material is removed from his sinuses and examined under the microscope. What is his diagnosis?
Mycetoma
Fungus ball (mycetoma, aspergilloma)
- Sinuses with poor drainage; fungi proliferate and form dense mass of hyphae
- DO NOT invade mucosa/vessels